Specific resting-state brain networks in mesial temporal lobe epilepsy.
We studied with functional magnetic resonance imaging (fMRI) differences in resting-state networks between patients with mesial temporal lobe epilepsy (MTLE) and healthy subjects. To avoid any a priori hypothesis, we use a data-driven analysis assessing differences between groups independently of structures involved. Shared and specific independent component analysis (SSICA) is an exploratory method based on independent component analysis, which performs between-group network comparison. It extracts and classifies components (networks) in those common between groups and those specific to one group. Resting fMRI data were collected from 10 healthy subjects and 10 MTLE patients. SSICA was applied multiple times with altered initializations and different numbers of specific components. This resulted in many components specific to patients and to controls. Spatial clustering identified the reliable resting-state networks among all specific components in each group. For each reliable specific network, power spectrum analysis was performed on reconstructed time-series to estimate connectivity in each group and differences between groups. Two reliable networks, corresponding to statistically significant clusters robustly detected with clustering were labeled as specific to MTLE and one as specific to the control group. The most reliable MTLE network included hippocampus and amygdala bilaterally. The other MTLE network included the postcentral gyri and temporal poles. The control-specific network included bilateral precuneus, anterior cingulate, thalamus, and parahippocampal gyrus. Results indicated that the two MTLE networks show increased connectivity in patients, whereas the control-specific network shows decreased connectivity in patients. Our findings complement results from seed-based connectivity analysis (1). The pattern of changes in connectivity between mesial temporal lobe structures and other areas may help us understand the cognitive impairments often reported in patients with MTLE.


Regular Vigorous-Intensity Physical Activity and Walking Are Associated with Divergent but not Convergent Thinking in Japanese Young Adults.
The beneficial effects of regular physical activity (PA) on cognitive functions have received much attention. Recent research suggests that regular PA may also enhance creative thinking, an indispensable cognitive factor for invention and innovation. However, at what intensity regular PA brings the most benefits to creative thinking remains uninvestigated. Furthermore, whether the levels of regular PA affect the acute PA effects on creative thinking is also unclear. In the present study, using a previous dataset that investigated the effects of an acute bout of aerobic exercise on creative thinking in healthy Japanese young adults (22.98 ± 1.95 years old) in the year 2020, we tested the association between different intensities of regular PA (i.e., vigorous, moderate, and walking) and creative thinking with the cross-sectional baseline data using multiple linear regression. We also investigated whether regular PA levels were associated with the acute aerobic exercise intervention effects on creative thinking. The results showed that cross-sectionally, the regular PAs were differentially associated with divergent but not convergent thinking. Specifically, whereas the amount of vigorous-intensity PA was positively associated with fluency and flexibility, the amount of walking was positively associated with novelty on the alternate uses test (AUT) measuring divergent thinking. Importantly, the explained variances of fluency, flexibility, and novelty were 20.3% (p = 0.040), 18.8% (p = 0.055), and 20.1% (p = 0.043), respectively. None of the regular PAs predicted convergent thinking (i.e., an insight problem-solving task), nor were they associated with the acute aerobic exercise intervention effects on divergent and convergent thinking. These findings suggest that engaging in regular vigorous-intensity PA and walking may be useful strategies to enhance different aspects of divergent thinking in daily life.


Regulation of islet beta-cell pyruvate metabolism: interactions of prolactin, glucose, and dexamethasone.
Prolactin (PRL) induces beta-cell proliferation and glucose-stimulated insulin secretion (GSIS) and counteracts the effects of glucocorticoids on insulin production. The mechanisms by which PRL up-regulates GSIS are unknown. We used rat islets and insulinoma (INS-1) cells to explore the interactions of PRL, glucose, and dexamethasone (DEX) in the regulation of beta-cell pyruvate carboxylase (PC), pyruvate dehydrogenase (PDH), and the pyruvate dehydrogenase kinases (PDKs), which catalyze the phosphorylation and inactivation of PDH. PRL increased GSIS by 37% (P < 0.001) in rat islets. Glucose at supraphysiological concentrations (11 mm) increased PC mRNA in islets; in contrast, PRL suppressed PC mRNA levels in islets and INS-1 cells, whereas DEX was without effect. Neither PRL nor DEX altered PC protein or activity levels. In INS-1 cells, PRL increased PDH activity 1.4- to 2-fold (P < 0.05-0.001) at glucose concentrations ranging from 2.5-11 mm. DEX reduced PDH activity; this effect was reversed by PRL. PDK1, -2, -3, and -4 mRNAs were detected in both islets and insulinoma cells, but the latter expressed trivial amounts of PDK4. PRL reduced PDK2 mRNA and protein levels in rat islets and INS-1 cells and PDK4 mRNA in islets; DEX increased PDK2 mRNA in islets and INS-1 cells; this effect was reversed by PRL. Our findings suggest that PRL induction of GSIS is mediated by increases in beta-cell PDH activity; this is facilitated by suppression of PDKs. PRL counteracts the effects of DEX on PDH and PDK expression, suggesting novel roles for the lactogens in the defense against diabetes.


Highly accurate first-principles benchmark data sets for the parametrization and validation of density functional and other approximate methods. Derivation of a robust, generally applicable, double-hybrid functional for thermochemistry and thermochemical kinetics.
We present a number of near-exact, nonrelativistic, Born-Oppenheimer reference data sets for the parametrization of more approximate methods (such as DFT functionals). The data were obtained by means of the W4 ab initio computational thermochemistry protocol, which has a 95% confidence interval well below 1 kJ/mol. Our data sets include W4-08, which are total atomization energies of over 100 small molecules that cover varying degrees of nondynamical correlations, and DBH24-W4, which are W4 theory values for Truhlar's set of 24 representative barrier heights. The usual procedure of comparing calculated DFT values with experimental atomization energies is hampered by comparatively large experimental uncertainties in many experimental values and compounds errors due to deficiencies in the DFT functional with those resulting from neglect of relativity and finite nuclear mass. Comparison with accurate, explicitly nonrelativistic, ab initio data avoids these issues. We then proceed to explore the performance of B2x-PLYP-type double hybrid functionals for atomization energies and barrier heights. We find that the optimum hybrids for hydrogen-transfer reactions, heavy-atoms transfers, nucleophilic substitutions, and unimolecular and recombination reactions are quite different from one another: out of these subsets, the heavy-atom transfer reactions are by far the most sensitive to the percentages of Hartree-Fock-type exchange y and MP2-type correlation x in an (x, y) double hybrid. The (42,72) hybrid B2K-PLYP, as reported in a preliminary communication, represents the best compromise between thermochemistry and hydrogen-transfer barriers, while also yielding excellent performance for nucleophilic substitutions. By optimizing for best overall performance on both thermochemistry and the DBH24-W4 data set, however, we find a new (36,65) hybrid which we term B2GP-PLYP. At a slight expense in performance for hydrogen-transfer barrier heights and nucleophilic substitutions, we obtain substantially better performance for the other reaction types. Although both B2K-PLYP and B2GP-PLYP are capable of 2 kcal/mol quality thermochemistry, B2GP-PLYP appears to be the more robust toward nondynamical correlation and strongly polar character. We additionally find that double-hybrid functionals display excellent performance for such problems as hydrogen bonding, prototype late transition metal reactions, pericyclic reactions, prototype cumulene-polyacetylene system, and weak interactions.


Matrix metalloproteinase-9 -1562T allele and its combination with MMP-2 -735 C allele are risk factors for breast cancer.
Expression of matrix metalloproteinases (MMPs) is up-regulated in human cancers. The aim of present study was to investigate the role of MMP-9 C-1562T polymorphism and its interaction with MMP- 2 C-735T polymorphism in susceptibility to breast cancer in a population from Western Iran with Kurdish ethnic background. The study sample of 205 individuals consisted of 101 breast cancer patients and 104 healthy subjects. MMP-9 C-1562T and MMP-2 C-735T variants were identified using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Among 67.4% of studied patients the breast cancer developed in the third and forth decades of the life. The frequency of MMP-9 T allele was 17.3% in patients and 10.1% in controls. The presence of T allele significantly increased the risk of breast cancer by 1.87-fold [OR=1.87 (95% CI 1.05-3.33, p=0.035)]. The frequency of MMP-9 CT+TT genotype tended to be higher in those patients with a family history of cancer in first degree-relatives (36.8%) than those without a family history (28.3%, p=0.37). We observed an interaction between the MMP-9 -1562 T allele with MMP-2 -735 C allele that significantly increased the risk of breast cancer [OR=1.42 (95% CI 1.02- 1.98, p=0.036)]. The present study demonstrated that MMP-9 C-1562T polymorphism alone and in combination with MMP-2 C-735T polymorphism increased the risk of breast cancer that might be a useful biomarker in identifying women at risk of developing breast cancer. Also, this study revealed that in most women from Western Iran breast cancer presents in third and fourth decades of life.


Inter-muscular adipose tissue is associated with adipose tissue inflammation and poorer functional performance in central adiposity.
The presence of concomitant sarcopenia and obesity in sarcopenic obesity (SO) confers worse functional, morbidity and mortality outcomes compared to either alone. Excess adiposity and central redistribution of fats are associated with systemic inflammation and ectopic tissue fat infiltration in forms of Intermuscular adipose tissue (IMAT). Our study examines the profile of IMAT across a spectrum of body compositions and associations with physical performance and inflammatory biomarkers including Monocyte Chemoattractant Protein-1 (MCP-1), a novel biomarker of adipose tissue inflammation. 187 community dwelling elderly participants were recruited and classified into 4 subgroups: normal, obese, sarcopenia and SO, using validated criteria for sarcopenia and waist circumference to define central obesity. We performed magnetic resonance imaging of mid-thigh sections to segment IMAT and muscle. Participants were assessed for muscle strength, physical performance and blood inflammatory biomarkers of interleukin-6, C-Reactive Protein and MCP-1. We examined correlation of IMAT(ratio) with muscle function measures and blood biomarkers. Multiple regression analyses were used to examine the association of body composition types and IMAT(ratio) with muscle function. IMAT(ratio) was highest in SO and obese groups. Overall, higher IMAT(ratio) is significantly associated with raised MCP-1, lower gait speed and muscle strength. SO had lowest scores in Short Physical Performance Battery (SPPB), gait speed, hand-grip and knee extension strength. IMAT(ratio) is independently associated with SPPB and handgrip strength, whilst SO is independently associated with muscle strength. Our results suggest the possible role of IMAT as a candidate imaging biomarker for adipose tissue inflammation and associated poorer functional outcomes in SO.


Thermal ablation of saphenous veins is feasible and safe in patients older than 75 years: A prospective study (EVTA study).
To investigate the tolerance and safety of thermal ablation (TA), consisting of radiofrequency or endovenous laser (EVLA) of saphenous veins (SV) in elderly (group 1 ≥75 years), compared with a control group (group 2 <75 years). An Observational multicenter-prospective study was conducted, under the aegis of the French and Swiss Societies of Phlebology (18 centers). Ninety patients were included in group 1, 617 in group 2 (mean age 80 years and 53 years; 69% women in both groups), representing 863 SV. Mean trunk diameters were similar in both groups (small SV: 6 mm; great SV: 7 mm). In group 1, comorbidities were more frequent, particularly cardiac insufficiency, diabetes, history of thrombosis, and CEAP clinical class was significantly higher. EVLA was used in 86% of cases. Settings used were similar in both groups for each technique. Only 6% of TA was performed in an operating room for group 1 (14% group 2). Tumescent local anaesthesia (TLA) alone was used in 91% of cases in group 1 (85% group 2). The mean pain score was only 1.6 for the procedure itself (VASP 0-10; 10 max.) and 1.4 for the 10 days following the procedure. Side effects were few, but rate of paraesthesia was higher when general anaesthesia was used (11.8%) compared with TLA alone (2.2%). At three months, 100% of SV was occluded in group 1 (99.5% group 2), with high satisfaction score (9.3/10). TA is safe and effective in elderly; it should be performed strictly under TLA to minimize side effects.


Concomitant bullous pemphigoid and dermatitis herpetiformis.
Dermatitis herpetiformis and bullous pemphigoid are bullous autoimmune diseases of the skin microscopically characterized by subepidermal blisters. We present a 77-year-old patient with an 18-month history of disseminated pruritic papular lesions. Direct immunofluorescence microscopy revealed linear deposition of IgG at the basement membrane zone as well as granular deposits of IgA in the papillary dermis. Circulating IgG antibodies against BP180, BP230 and gliadin as well as IgA reactivity against endomysium, tissue transglutaminase, and gliadin were detected compatible with both bullous pemphigoid and dermatitis herpetiformis. Here, we review the English literature on all previously reported patients with co-occurrence of both entities. Interestingly, in previous cases, tissue-bound and serum autoantibodies against the respective target antigens had not yet been completely characterized.


Significance of continuous medical education of general practitioners about common diseases--iron deficiency anemia.
Three years long, prospective study was performed in order to evaluate a possible influence of continuing medical education of general practitioners on managing the patients with common diseases such as iron deficiency anemia (IDA). Altogether 1586 patients that were referred to Hematology Outpatient Clinic, University Hospital Center Rtjeka, Croatia due to diagnosis of IDA were examined by clinical hematologist during the first visit and follow up period, were questioned by the means of questionnaire and complete laboratory analyzes were performed in order to: evaluate physical condition and laboratory findings, to assess duration of anemia, possible other specialists' consultation, iron supplementation therapy, and finally, determine the type of anemia present. Initial group of 983 patients was examined during one year period. Following the education campaign the same parameters were analyzed in comparable (final) group of 603 patients during next one year period. Following the education, the number of patients referred to Outpatient Clinic due to diagnosis of IDA was significantly decreased from 983 (61.97%) to 603 (38.02%) (p < 0.05) as was the number of patients referred as having IDA but finally established to have a different type of anemia, from 661 (97.24%) to 149 (24.71%) (p < 0.001). The number of patients started on iron supplementation therapy before establishing the type of anemia was significantly decreased from 543 (55.24%) to 76 (12.60%) (p < 0.001) as well as duration of iron supplementation therapy administered in these cases (21 +/- 9.8 vs. 6 +/- 8.7 weeks) (p < 0.001). We have detected a significant decrease in: time necessary for definitive diagnosis (49 +/- 19.2 vs. 28 +/- 9.1 weeks) (p < 0.001), number of visits to other specialists (2.9 +/- 1.35 vs. 1.1 +/- 0.94) (p < 0.05), duration of anemia before treatment initialization (41 +/- 29.8 vs. 26 +/- 18.7 weeks) (p < 0.001). Average hemoglobin (Hg) level in patients referred to hematologist was significantly lower following education (98.9 +/- 15.5 vs. 82.6 +/- 14.2) (p < 0.05). Continuing medical education of primary care physicians has significant role in diagnosis and treatment of patients with IDA. Education programs result in benefits for the patients and physicians.


A method for automatic detection and classification of stroke from brain CT images.
Computed tomographic (CT) images are widely used in the diagnosis of stroke. In this paper, we present an automated method to detect and classify an abnormality into acute infarct, chronic infarct and hemorrhage at the slice level of non-contrast CT images. The proposed method consists of three main steps: image enhancement, detection of mid-line symmetry and classification of abnormal slices. A windowing operation is performed on the intensity distribution to enhance the region of interest. Domain knowledge about the anatomical structure of the skull and the brain is used to detect abnormalities in a rotation- and translation-invariant manner. A two-level classification scheme is used to detect abnormalities using features derived in the intensity and the wavelet domain. The proposed method has been evaluated on a dataset of 15 patients (347 image slices). The method gives 90% accuracy and 100% recall in detecting abnormality at patient level; and achieves an average precision of 91% and recall of 90% at the slice level.


Bidirectional interactions between bone metabolism and hematopoiesis.
Interactions between hematopoiesis and bone metabolism have been described in various developmental and pathological situations. Here we review this evidence from the literature with a focus on microenvironmental regulation of hematopoiesis and bone metabolism. Our hypothesis is that this process occurs by bidirectional signaling between hematopoietic and mesenchymal cells through cell adhesion molecules, membrane-bound growth factors, and secreted matrix proteins. Examples of steady-state hematopoiesis and pathologies are presented and support our view that hematopoietic and mesenchymal cell functions are modulated by specific microenvironments in the bone marrow.


Persisting ring chromosomes detected by mFISH in lymphocytes of a cancer patient-a case report.
We report the case of an 84 years old prostate cancer patient with severe side effects after radiotherapy in 2006. He was cytogenetically analysed in 2009 and in 2012 in a comparative study for individual radiosensitivity of prostate cancer patients. No other patient had clonal aberrations, but this patient showed ring chromosomes in the range of 21-25% of lymphocytes. He received 5 cycles of 5-fluorouracil/folic acid for chemotherapy of sigmoid colon carcinoma in 2003, three years before radiotherapy of prostate cancer. Blood samples were irradiated ex vivo with Cs-137 γ-rays (0.7Gy/min) in the G0-phase of the cell cycle. 100 FISH painted metaphases were analysed for the control and the irradiated samples each. Multicolour in situ hybridisation techniques like mFISH and mBand as well as MYC locus, telomere and centromere painting probes were used to characterise ring metaphases. Metaphase search and autocapture was performed with a Zeiss Axioplan 2 imaging microscope followed by scoring and image analysis using Metafer 4/ISIS software (MetaSystems). In 2009 chromosome 8 rings were found in about 25% of lymphocytes. Rings were stable over time and increased to about 30% until 2012. The ring chromosome 8 always lacked telomere signals and a small amount of rings displayed up to four centromere signals. In aberrant metaphases 8pter and 8qter were either translocated or deleted. Further analyses revealed that the breakpoint at the p arm is localised at 8p21.2-22. The breakpoint at the q arm turned out to be distal from the MYC locus at 8q23-24. We hypothesise that the ring chromosome 8 has been developed during the 5 FU/folic acid treatments in 2003. The long term persistence might be due to clonal expansion of a damaged but viable hematopoietic stem cell giving rise to cycling progenitor cells that permit cell survival and proliferation.


Local circuit synaptic interactions in hippocampal brain slices.
The hypothesis that recurrent inhibition in the hippocampus is mediated by interneurons was tested with simultaneous intracellular recordings from the CA1 region of guinea pig hippocampal slices in vitro. In recordings from 101 pairs of pyramidal cells, no interactions were detected in 87% of the pairs. In 13% of the pyramidal cell pairs, spike trains induced in one cell caused inhibitor postsynaptic potentials (IPSPs) in the second cell. No excitatory interactions were detected. In recordings from 43 pairs of cells, where one cell was a pyramidal cell and the other cell was an interneuron, no interactions were detected in 53% of the pairs. In 30% of the interneuron-pyramidal cell pairs, spike trains elicited from the interneuron caused IPSPs in the pyramidal cell. In 28% of the pairs, spike trains elicited from the pyramidal cell caused excitatory postsynaptic potentials (EPSPs) in the interneurons. In 4% of these pairs, reciprocal interactions were seen, with the pyramidal cell exciting the interneuron and the interneuron inhibiting the pyramidal cell. These results support the hypothesis that inhibitory mediate recurrent inhibition in the hippocampus. However, the data also suggest that the interneurons from which these results were recorded were a subset of inhibitory interneurons distinct from the classical basket cell. These interneurons may mediate both feed-forward and recurrent inhibition in the hippocampus.


HDSCC: A robust clustering approach for Single Cell RNA-seq data using Hyperdimensional Encoding.
Significant improvement in Single Cell technologies has given a hand to researchers to measure RNA expression of considerable number of Single Cells simultaneously, resulting in noticeable progress in our knowledge of cellular structure. Microfluidics-based sequencing protocols employing unique molecular identifiers (UMIs) lead to not only high-quality processing but also screening of thousands of cells. However, analysis of said data has caused challenges when it comes to processing time and computational resources as well as analyzing noisy and highly sparse data. Addressing these issues, we proposed a new method to cluster large RNA-seq datasets effectively. In our proposed approach, for having a noise robust clustering, we employed Hyper Dimensional Computing (HDC) approach to analyze Single Cell RNA sequencing data for the first time as best of our knowledge. We compared our results with state-of-the-art works on single-cell clustering and it shows promising performance and robustness in comparison to them. We performed our experiments with a 3.2-GHz CPU and 32 GB of RAM laptop.


Do We Really Need to Worry About Calcaneocuboid Subluxation During Lateral Column Lengthening for Planovalgus Foot Deformity?
Although lengthening of the lateral column through an osteotomy of the anterior calcaneus is an integral component of flatfoot reconstruction in younger patients with flexible planovalgus deformities, the procedure has been implicated in iatrogenic calcaneocuboid (CC) subluxation and subsequent degenerative changes at the CC articulation. The purpose of this study is to characterize alterations at the CC joint after lateral column lengthening (LCL) and determine if Steinmann pin stabilization of the CC joint before distraction maintains a normal relationship. Seven matched pairs of fresh-frozen cadaveric feet underwent preprocedure plain radiography and cross-sectional computed tomography (CT) imaging. LCL by osteotomy through the anterior calcaneus was then performed. One foot of each matched pair had a single smooth Steinmann pin placed centrally across the CC joint before osteotomy distraction. Distraction across each osteotomy was then performed and maintained with a 12-mm porous titanium wedge. Repeat imaging was obtained and compared with preprocedure studies to quantify sagittal and rotational differences at the CC articulation. Following LCL, plain radiography demonstrated statistically significant increases in the percentage of the calcaneal articular surface dorsal to the superior aspect of the cuboid in both the pinned (8.2% vs. 17.6%, P=0.02) and unpinned (12.5% vs. 16.3%, P=0.04) specimens. No difference in the percentage of subluxation was found between the 2 groups after LCL. CT imaging demonstrated statistically significant increases in rotation between the calcaneus and cuboid after LCL in both the pinned (7.6±5.6 degrees, P=0.01) and unpinned (17±12.3 degrees, P=0.01) specimens. The degree of rotation was greater in unpinned specimens after LCL (P=0.043). Both sagittal and rotatory subluxation seem to occur at the CC joint after LCL regardless of pin stabilization. As a single pin would be expected to limit pure translation while having little effect on rotation, it is possible that the rotational changes identified on 3-dimensional imaging are interpreted as dorsal translation when viewed 2 dimensionally using plain radiography. Consideration should therefore be given to CC stabilization with 2 pins during LCL to prevent this rotatory subluxation. Level V-cadaver study.


Deletion of gpUL132, a structural component of human cytomegalovirus, results in impaired virus replication in fibroblasts.
The coding capacity of human cytomegalovirus (HCMV) for glycoproteins by far exceeds that of other herpesviruses. Few of these proteins have been characterized so far. We have investigated the gene product of reading frame UL132. The putative protein product of UL132 is a glycoprotein with a theoretical mass of 29.8 kDa. Transcription analysis revealed that the gene is transcribed with a true late kinetics from the laboratory-adapted strain AD169 and the low-passage isolate TB40E. Two proteins of 22 to 28 kDa and 45 to 60 kDa were detected in virus-infected cells as well as in extracellular virions. The larger protein carried N-linked carbohydrates. Both protein forms were present in laboratory-adapted strains as well as in low-passage isolates of HCMV. Recombinant viruses with the UL132 gene deleted were constructed in the low-passage HCMV isolate PAN as well as the high-passage isolate AD169. Deletion of UL132 from either genome resulted in a pronounced replication deficit with a reduction of approximately 100-fold for HCMV strain AD169. Thus, the protein product of the UL132 reading frame represents a structural viral glycoprotein of HCMV that has an important function for viral replication in tissue culture.


Postnatal changes in the developing rat extraocular muscles.
To examine the distribution and timing of expression of nonmuscle myosin IIB (nmMyH IIB) and the extraocular muscle (EOM)-specific myosin (EO-MyHC) during postnatal development of the rat extraocular muscles. Whole orbits were collected from postnatal development day (P) 1 through P30 from Sprague-Dawley rats. Samples were analyzed by immunofluorescence microscopy and Western blot to examine the distribution and abundance of nmMyH IIB and EO-MyHC compared with other myosin isoforms and sarcomeric α-actinin. Polyclonal antibodies were produced to specifically detect EO-MyHC. Postnatal limb muscles were used as control. Analysis of EOM morphology in the developing orbits indicates that the global and orbital layers are not evident until day P15. The distribution of nmMyH IIB changes between days P10 and P15 from a subsarcolemma distribution to an intrafiber distribution in the global layer. EO-MyHC appears by day p15, primarily in the orbital layer of the EOMs. Sarcomeric α-actinin was equally abundant in the EOMs at all stages. Fetal MyHC was the predominant isoform at day P1 but slowly diminished in abundance with age in a layer-specific manner. These data demonstrate that significant changes occur in the EOMs from P10 to P15 and suggest that visual stimulation may play a role in the signals that regulate both nmMyH IIB and EO-MyHC developmental transitions. The pronounced distinctions of the orbital and global layers occurring by P15 establish the adult morphologic phenotype of the muscle.


Measuring Global Brain Atrophy with the Brain Volume/Cerebrospinal Fluid Index: Normative Values, Cut-Offs and Clinical Associations.
Global brain atrophy is present in normal aging and different neurodegenerative disorders such as Alzheimer's disease (AD) and is becoming widely used to monitor disease progression. The brain volume/cerebrospinal fluid index (BV/CSF index) is validated in this study as a measurement of global brain atrophy. We tested the ability of the BV/CSF index to detect global brain atrophy, investigated the influence of confounders, provided normative values and cut-offs for mild, moderate and severe brain atrophy, and studied associations with different outcome variables. A total of 1,009 individuals were included [324 healthy controls, 408 patients with mild cognitive impairment (MCI) and 277 patients with AD]. Magnetic resonance images were segmented using FreeSurfer, and the BV/CSF index was calculated and studied both cross-sectionally and longitudinally (1-year follow-up). Both AD patients and MCI patients who progressed to AD showed greater global brain atrophy compared to stable MCI patients and controls. Atrophy was associated with older age, larger intracranial volume, less education and presence of the ApoE ε4 allele. Significant correlations were found with clinical variables, CSF biomarkers and several cognitive tests. The BV/CSF index may be useful for staging individuals according to the degree of global brain atrophy, and for monitoring disease progression. It also shows potential for predicting clinical changes and for being used in the clinical routine.


The functional age of hearing loss in a mouse model of presbycusis. I. Behavioral assessments.
Presbycusis is a common form of hearing loss that progresses from high to low frequencies with advancing age. C57BL/6J mice experience a rapid progression of presbycusis-like hearing deficits and thus provide a convenient animal model for evaluating behavioral, physiological and anatomical correlates of the disorder. Previous studies of C57BL/6J mice have relied on short-term observations of age-matched subject groups to reconstruct a time course for auditory pathologies. Such statistical approaches are weakened by the variability of hearing thresholds in young mice and the inconsistent timing of degenerative effects in older mice. The present study was designed to resolve these ambiguities by tracking the hearing abilities of individual C57BL/6J mice from age 16 weeks until the onset of hearing loss in specific listening conditions. Testing at frequencies of 8 and 16 kHz in quiet confirmed the high-to-low frequency progression that is characteristic of presbycusis. Often the hearing loss developed in two phases, one gradual and the other abrupt. Testing in noise revealed deficits that were first manifested as threshold instability and then an increased susceptibility to masking. These changes occurred before hearing loss in quiet. CBA/CaJ mice did not show significant loss during a similar period of observation. Our findings provide a well-ordered chronology for isolating the functional consequences of multiple cochlear pathologies that arise during the time course of presbycusis. This neurobehavioral assessment is termed the functional age of hearing loss. Neuroanatomical assessments of behaviorally characterized C57BL/6J mice are presented in the companion paper [Hear. Res. 183 (2003) 29-36].


The environmental impact of mask-derived microplastics on soil ecosystems.
During the COVID-19 pandemic, a significant increased number of masks were used and improperly disposed of. For example, the global monthly consumption of approximately 129 billion masks. Masks, composed of fibrous materials, can readily release microplastics, which may threaten various soil ecosystem components such as plants, animals, microbes, and soil properties. However, the specific effects of mask-derived microplastics on these components remain largely unexplored. Here, we investigated the effects of mask-derived microplastics (grouped by different concentrations: 0, 0.25, 0.5, and 1 % w/w) on soil physicochemical properties, microbial communities, growth performance of lettuce (Lactuca sativa L. var. ramosa Hort.) and earthworm (Eisenia fetida) under laboratory conditions for 80 days. Our findings suggest that mask-derived microplastics reduced soil bulk density while increasing the mean weight diameter of soil aggregates and modifying nutrient levels, including organic matter, potassium, nitrogen, and phosphorus. An increase in the abundance of denitrification bacteria (Rhodanobacteraceae) was also observed. Mask-derived microplastics were found to reduce lettuce germination, and a hormesis effect of low-concentration stimulation and high-concentration inhibition was observed on biomass, chlorophyll, and root activity. While the mortality of earthworms was not significantly affected by the mask-derived microplastics, but their growth was inhibited. Collectively, our results indicate that mask-derived microplastics can substantially impact soil properties, plant growth, and earthworm health, with potential implications for soil ecosystem functionality.


Effects of orchidectomy in selective biochemical analytes in Beagle dogs.
The objective of this study was to evaluate the possible effects of orchidectomy and associate hormonal changes on circulating concentrations of acute-phase proteins (APPs) (CRP--C-reactive protein; Hp--haptoglobin; Cp--ceruloplasmin), adiponectin and IGF-1 in dogs. For this, a total of five adult Beagle dogs were subjected to orchidectomy. Blood samples were taken before neutering, during six consecutive days and on weeks 2, 4, 8 and 12 after surgery. Appropriate diet regime was maintained to keep stable body weight of the dogs. Concentrations of APPs significantly increased on days 2-3 for CRP and 2-7 for Hp and Cp. On days 3-4 after neutering, adiponectin levels were significantly lower than before surgery (p<0.05 and <0.01, respectively). After this initial change, adiponectin did not show any significant alteration during the 3 months. Serum IGF-1 concentrations were significantly decreased at days 2-5 after neutering. In addition, on weeks 8 and 12 serum IGF-1 levels were significantly lower (p<0.001 and <0.01 respectively) in comparison with those before surgery. In conclusion, orchidectomy induced a short-term inflammatory process that was associated with the increase in serum levels of APPs and decrease in IGF-1 and adiponectin levels. However, orchidectomy did not result in long-term changes of circulating concentrations of APPs or adiponectin. Although a decrease in IGF-1 levels was recorded 2 months after surgery, possibly as a consequence of associated decrease in androgen levels or food restriction.


Postoperative Pain, an Unmet Problem in Day or Overnight Italian Surgery Patients: A Prospective Study.
Background. Because of economic reasons, day surgery rates have steadily increased in many countries and the trend is to perform around 70% of all surgical procedures as day surgery. Literature shows that postoperative pain treatment remains unfulfilled in several fields such as orthopedic and general surgery patients. In Italy, the day surgery program is not yet under governmental authority and is managed regionally by local practices. Aim. To investigate the trends in pain intensity and its relation to type of surgeries and pain therapy protocols, in postoperative patients, discharged from three different Ambulatory Surgeries located in North West Italy (Piedmont region). Method. The present study enrolled 276 patients who undergone different surgical procedures in ambulatory regimen. Patients recorded postoperative pain score twice a day, compliance with prescribed drugs, and pain related reasons for contacting the hospital. Monitoring lasted for 7 days. Results. At discharge, 72% of patients were under weak opioids, 12% interrupted the treatment due to side effects, 17% of patients required extra drugs, and 15% contacted the hospital reporting pain problems. About 50% of patients experienced moderate pain during the first day after surgery. Results from our study show that most of the patients experienced avoidable pain after discharge.


Excessive fluid accumulation during stem cell mobilization: a novel prognostic factor of first-year survival after stem cell transplantation in AL amyloidosis patients.
High-dose melphalan followed by stem cell transplantation (HDM-SCT) has become the treatment of choice for patients with immunoglobulin light chain amyloidosis (AL). Unfortunately, treatment mortality can be excessive in certain subpopulations. We have noted that patients who gained more than 2% body weight during mobilization had a poorer outcome following HDM-SCT. Excluding 2 patients for lack of weight record and denial of consent, 126 patients between July 1997 and June 2003 were retrospectively studied. Weight increased more than 2.0% during mobilization in 51.6% of the patients. Patients who accumulated more than 2.0% tended to have more proteinuria, more organs involved, lower serum albumin, more diuretic use, and dosage adjustment during mobilization. First-year mortality was significantly higher in those with more than 2% weight gain (33.9% versus 9.8%, P = .002). Multivariate analysis showed weight gain, glomerular filtration rate, and septal thickness to be independent predictors of first-year mortality. The increase in mortality was noted even after the excess weight was diuresed prior to conditioning. The impact on mortality dissipated after the first year. Weight gain during mobilization appears to be a new marker of adverse outcome following HDM-SCT. Better prognostication may improve the treatment mortality rate of these patients.


Transcript profiles of Candida albicans cortical actin patch mutants reflect their cellular defects: contribution of the Hog1p and Mkc1p signaling pathways.
In Candida albicans, Myo5p and Sla2p are required for the polarized localization and function of cortical actin patches, for hyphal formation, and for endocytosis. Deletion of either the MYO5 or the SLA2 gene generated a common transcriptional response that involved changes in the transcript levels of cell wall protein- and membrane protein-encoding genes. However, these profiles were distinct from those observed for a mutant with specific deletions of the actin-organizing domains of Myo5p or for wild-type cells treated with cytochalasin A, both of which also generate defects in the organization of cortical actin patches. The profiles observed for the myo5Delta and sla2Delta mutants had similarities to those of wild-type cells subjected to an osmotic shock, and the defects in cortical patch function found with myo5Delta and sla2Delta mutants, but not cortical actin patch distribution per se, affected sensitivity to various stresses, including heat and osmotic shocks and cell wall damage. Secondary effects coupled with defective endocytosis, such as lack of polarized lipid rafts and associated protein Rvs167-GFP (where GFP is green fluorescent protein) and lack of polarized wall remodeling protein GFP-Gsc1, were also observed for the myo5Delta and sla2Delta mutants. The mitogen-activated protein kinases Hog1p and Mkc1p, which mediate signaling in response to osmotic stress and cell wall damage, do not play a major role in regulating the transcript level changes in the myo5Delta and sla2Delta mutants. Hog1p was not hyperphosphorylated in the myo5Delta and sla2Delta mutants, and the transcript levels of only a subset of genes affected in the myo5Delta mutant were dependent upon the presence of Hog1p and Mkc1p. However, it appears that Hog1p and Mkc1p play important roles in the myo5Delta mutant cells because double deletion of myosin I and either Hog1p or Mkc1p resulted in very-slow-growing cells.


Self-protection strategies and health behaviour in patients with inflammatory rheumatic diseases during the COVID-19 pandemic: results and predictors in more than 12 000 patients with inflammatory rheumatic diseases followed in the Danish DANBIO registry.
In Danish patients with inflammatory rheumatic diseases to explore self-protection strategies and health behaviour including adherence to disease-modifying antirheumatic treatment (DMARD) during the initial phase of the COVID-19 pandemic and again after the reopening of the society started. Furthermore, to identify characteristics of patients with high levels of anxiety and self-isolation. Patients in routine care followed prospectively in the nationwide DANBIO registry were invited to answer an online questionnaire regarding disease activity and COVID-19 infection, behaviour in March and June 2020. Responses were linked to patient data in DANBIO. Characteristics potentially associated with anxiety, self-isolation and medication adherence (gender/age/diagnosis/education/work status/comorbidity/DMARD/smoking/EQ-5D/disease activity) were explored with multivariable logistic regression analyses. We included 12 789 patients (8168 rheumatoid arthritis/2068 psoriatic arthritis/1758 axial spondyloarthritis/795 other) of whom 65% were women and 36% treated with biological DMARD. Self-reported COVID-19 prevalence was 0.3%. Patients reported that they were worried to get COVID-19 infection (March/June: 70%/45%) and self-isolated more than others of the same age (48%/38%). The fraction of patients who changed medication due to fear of COVID-19 were 4.1%/0.6%. Female gender, comorbidities, not working, lower education, biological treatment and poor European Quality of life, 5 dimensions were associated with both anxiety and self-isolation. In >12 000 patients with inflammatory arthritis, we found widespread anxiety and self-isolation, but high medication adherence, in the initial phase of the COVID-19 pandemic. This persisted during the gradual opening of society during the following months. Attention to patients' anxiety and self-isolation is important during this and potential future epidemics.


Are people with mild cognitive impairment aware of the benefits of errorless learning?
Mild cognitive impairment (MCI) has been described as a memory deficit in the absence of other cognitive dysfunction. It can be thought of as a pre-clinical dementia. Memory impairment in this group is not as severe as in early dementia and thus learning is still possible. We were interested to see if errorless learning, a widely used rehabilitation technique, was of benefit to people with MCI. Since it has been shown that successful rehabilitation is somewhat contingent on awareness of function, we were also interested to see if people with MCI were aware of the benefits of errorless learning. The present study employed an errorless learning procedure on 16 people with MCI and 16 older adult controls to learn two lists of 10 words in errorless and errorful learning conditions. We adopted a metacognitive approach measuring people's memory monitoring through judgements of learning (JOLs) a prediction of future memory performance. The results revealed errorless learning is an effective memory rehabilitation tool for people with MCI, with significant increases in recall performance for both groups relative to errorful learning. Most interestingly participants were aware of the benefits of errorless learning in their JOLs. MCI participants and controls both had significantly higher JOLs for words studied under errorless learning conditions. The learning performance in MCI and theories of metacognitive awareness are discussed.


A comparison of smoking related attitudes and behaviors among Kentucky public school children whose families are and are not involved in tobacco production.
School health education has an important role to play in discouraging teenage smoking. However, it is likely that government, the general public and students themselves will be less favorable toward smoking education in major tobacco-producing states. To determine whether students whose families are involved in tobacco production hold more favorable attitudes toward smoking and smoke more than children whose families are not involved, 1,322 Kentucky public school students in grades five-12 were surveyed regarding smoking attitudes and behavior. Twenty-one percent (276) of the students reported that their families were involved in tobacco production. Tobacco family students held more favorable attitudes toward smoking and a larger percentage of these children smoked and smoked more than their nontobacco family peers. These differences were statistically significant at the 0.05 level. Tobacco family children appear to be at high risk for smoking-related disease and may prove resistant to some antismoking messages. Developing effective smoking education programs in major tobacco states in an important challenge for school health education.


Left Atrial Thrombus Mimicking Myxoma Secondary to Rebound Hypercoagulable State.
Novel oral anticoagulants (NOACs) have made the use of anticoagulation in patients with atrial fibrillation (AFib) much more convenient and predictable. It is a very common practice to hold anticoagulation either in anticipation of surgical procedures (to prevent excessive bleeding) or in case of acute bleeding episodes. This abrupt withdrawal of anticoagulation tilts the balance in favor of pro-thrombotic state in the body. We present a case of a 60-year-old man with past medical history of AFib who abruptly discontinued his apixaban (Eliquis). This patient presented to emergency room with the complaint of weakness and numbness of left arm and left half of the face. Stroke code was activated, and patient received tissue plasminogen activator (t-PA). This resulted in significant improvement of symptoms within hours of receiving treatment. Later during the same day, patient developed numbness and tingling of fingers of left hand. On physical exam, left hand was cold to touch and radial pulse was absent. Arterial duplex revealed occluded ulnar and radial arteries. Vascular surgery performed embolectomy to establish blood flow in the radial and ulnar arteries. Transthoracic echocardiogram revealed large left atrial mass attached to the atrial septum. Most likely t-PA infusion in the setting of atrial mass led to distal showering of emboli resulting in stenosis of radial and ulnar arteries. The left atrial mass was most likely thrombus as patient had cardiac imaging including transthoracic echocardiogram and computed tomography of heart prior to these events which did not reveal any mass in left atrium. In short, as clinicians we should be aware of the hypercoagulability associated with withdrawal of anticoagulation. In addition, we should be wary of the challenges associated with differentiating cardiac masses of different etiology.


The role of percutaneous transhepatic abscess drainage for liver abscess.
To evaluate the efficacy of percutaneous transhepatic abscess drainage (PTAD) as an initial choice of treatment for liver abscess, the medical records of 28 patients with liver abscess were retrospectively analyzed. The patients were predominantly men (23 of 28) with a mean age of 59 years (range, 19-86 years). Their chief complaints were fever (86%), right hypochondralgia (32%), and jaundice (11%). Fifteen of the 28 patients (54%) had hepatobiliary and pancreatic carcinoma, and 31% had postoperative liver abscess. PTAD was performed in 23 patients and surgical drainage in 5. The overall success rate for PTAD was 83%. The success rate for PTAD for patients with multiple abscesses was 83% (5 of 6), compared with a success rate of 82% (14 of 17) for patients with solitary abscess. The prognostic factors for survival were cancer and sepsis and the mortality rate for patients with cancer was 40% (6 of 15) while the mortality rate for patients with sepsis was 56% (5 of 9). As a complication of drainage, 1 patient (4%) in the PTAD group had pleural abscess due to the transpleural puncture. Our findings support the use of PTAD as the primary treatment for liver abscess, as it is safe and effective irrespective of the number of abscesses and the patient's condition.


An application of a diabetes knowledge scale for low-literate Hispanic/Latinos.
The threefold purpose of this study is to assess diabetes knowledge among Hispanic/Latinos attending a culturally sensitive, empowerment-based, diabetes self-management education program; second, to examine the utility of the Spoken Knowledge in Low Literacy in Diabetes (SKILLD) scale as an assessment tool for this population; and third, to assess the relationship between hemoglobin A1C and knowledge improvement in the intervention group. A prospective, quasi-experimental, repeated-measure design tested pre- and post-A1C and diabetes knowledge using the SKILLD scale. The sample consisted of 71 in the intervention group and 64 controls. Most participants were female, marginally acculturated, and, on average, 60 years of age. Both groups were similar in baseline diabetes knowledge score (median 6 out of 10), and higher literacy was significantly related to increased baseline knowledge. The intervention group significantly improved at follow-up compared with the controls: Participants in the intervention with low baseline knowledge scores had a mean follow-up score of 5.6; those with a high baseline score had a mean score of 7.6. The intervention cohort scored significantly better in knowing why to see an eye doctor, what are normal fasting blood glucose and A1C, and understanding long-term diabetes complications. Increased knowledge of a normal fasting blood glucose level had a significant effect on follow-up A1C in the intervention group. The intervention favorably affects diabetes knowledge, and the SKILLD scale has utility with low-literate Hispanic/Latinos. The significant impact on A1C by diabetes knowledge gain shows that the empowerment-based diabetes self-management education was successful for this ethnic population.


Activation of the unfolded protein response by deltaF508 CFTR.
Environmental insults and misfolded proteins cause endoplasmic reticulum (ER) stress and activate the unfolded protein response (UPR). The UPR decreases endogenous cystic fibrosis transmembrane conductance regulator (CFTR) mRNA levels and protein maturation efficiency. Herein, we investigated the effects of the folding-deficient deltaF508 CFTR on ER stress induction and UPR activation. For these studies, we developed and characterized stable clones of Calu3deltaF cells that express different levels of endogenous wild-type (WT) and recombinant deltaF508 CFTR. We also present a novel RT-PCR-based assay for differential quantification of wild-type CFTR mRNA in the presence of deltaF508 CFTR message. The assay is based on a TaqMan minor groove binding (MGB) probe that recognizes a specific TTT sequence (encoding phenylalanine at position 508 in human CFTR). The MGB probe is extremely specific and sensitive to changes in WT CFTR message levels. In RNA samples that contain both WT and deltaF508 CFTR mRNAs, measurement of WT CFTR mRNA levels (using the MGB probe) and total CFTR mRNA (using commercial primers) allowed us to calculate deltaF508 CFTR mRNA levels. The results indicate that overexpression of deltaF508 CFTR causes ER stress and activates the UPR. UPR activation precedes a marked decrease in endogenous WT CFTR mRNA expression. Furthermore, polarized airway epithelial cell lines are important tools in cystic fibrosis research, and herein we provide an airway epithelial model to study the biogenesis and function of WT and deltaF508 CFTR expressed within the same cell.


Cloning of deoxyribonucleic acid regions encoding a heat-labile and heat-stable enterotoxin originating from an enterotoxigenic Escherichia coli strain of human origin.
A heat-labile and heat-stable enterotoxin (LT+ ST+) plasmic (62.7 kilobases in size) was isolated from an enterotoxigenic Escherichia coli human strain, H10407, and used for analysis of the LT+ and ST+ deoxyribonucleic acid (DNA) regions. A DNA segment containing the LT+ and ST+ DNA regions, which consisted of two restriction endonuclease EcoRI fragments (E1 and E2), was inserted into the cloning vehicle ColE1::Tn5 by EcoRI digestion and subsequent ligation. Further cloning experiments localized the LT+ DNA region on a 5.1-kilobase restriction endonuclease PstI fragment present over the junction between the E1 and E2 fragments, as seen in the original LT+ ST+ plasmid, and the ST+ DNA region on a 1.5-kilobase PstI fragment present in either the E1 or E2 fragment. A change in the relative orientation of the E1 and E2 fragments resulted in altered levels of LT production. The relative orientation of the ColE1::Tn5 fragment to the E1 and E2 fragments also markedly influenced both LT and ST production levels. The LT+ ST+ E1-E2 region contained two unique DNA sequences consisting of a DNA segment flanked by inverted repeats which were readily distinguished from each other by size. The cloned ST+ PstI fragment was structurally very similar to one of these unique DNA sequences present in the LT+ ST+ E1-E2 region.


A minimized motile machinery for Mycoplasma genitalium.
The cell wall-less bacterium Mycoplasma genitalium uses specialized adhesins located at the terminal organelle to adhere to host cells and surfaces. The terminal organelle is a polar structure protruding from the cell body that is internally supported by a cytoskeleton and also has an important role in cell motility. We have engineered a M. genitalium null mutant for MG491 protein showing a massive downstream destabilization of proteins involved in the terminal organelle organization. This mutant strain exhibited striking similarities with the previously isolated MG_218 null mutant strain. Upon introduction of an extra copy of MG_318 gene in both strains, the amount of main adhesins P140 and P110 dramatically increased. These strains were characterized by microcinematography, epifluorescence microscopy and cryo-electron microcopy, revealing the presence of motile cells and filaments in the absence of many proteins considered essential for cell adhesion and motility. These results indicate that adhesin complexes play a major role in the motile machinery of M. genitalium and demonstrate that the rod element of the cytoskeleton core is not the molecular motor propelling mycoplasma cells. These strains containing a minimized motile machinery also provide a valuable cell model to investigate the adhesion and gliding properties of this human pathogen.


Exchange coupling constants using Density Functional Theory: long-range corrected functionals.
The presence of the self-interaction error in common exchange correlation functionals is one of the main drawbacks of calculations using methods based on Density Functional Theory. The recently developed asymptotically corrected functionals are an alternative way to solve the erroneous asymptotic behavior that may be at the origin of this error. Some of these functionals have been tested in the calculation of the exchange coupling constants of a number of transition metal dinuclear complexes. Correction of the self-interaction error is especially important for calculations of this kind. This error leads to the inclusion of some static correlation terms that overestimate the J values. This study shows that some of the long-range corrected functionals tested give promising results.


Melanocyte repopulation in full-thickness wounds using a cell spray apparatus.
Melanocyte restoration is critical in reconstituting skin color. We developed a spotted (piebald) pig wound model to study methods of restoring melanocytes to the epidermis. Paired, full-thickness, porcine wounds were covered with nonpigmented, fully expanded, 3:1 meshed, split-thickness skin grafts and were sprayed with an epidermal cell suspension. The suspensions were highly pigmented skin (HPS) cell isolates for half of the wounds (n = 16) and nonpigmented skin (NPS) cell isolates for the remaining wounds (n = 16). Histologic sections showed 6.0 +/- 3.0 and 15 +/- 4.0 pigmented melanocytes per high-power field on days 8 and 20 in HPS-treated wounds and no pigmented melanocytes in NPS-treated wounds. Melanin pigment was dispersed in all layers of the epithelium for the HPS group on day 20 compared with a lack of melanin pigment observed in the NPS group. Cell spraying may provide a clinical method to restore color to skin; further work is needed to control the expression of melanin.


[Effect of phospholipase on cation-induced transmembrane transport of DNA in Escherichia coli].
Incubation of bacterial cells in 0.1 M CaCl2 at 0 degrees C considerably increases the amount of phospholipids susceptible to action of a specific enzyme of phospholipid metabolism phospholipase C (hydrolysis to diacylglycerides). In process of incubation in CaCl2 solutions at 0 degrees C the expressed activity of an endogenous enzyme phospholipase A has been registered in cellular samples. Binding of the enzyme by the cells under conditions unfavourable for phospholipids hydrolysis (0 degrees C) suppresses strongly and reversibly cellular ability to DNA transformation without affecting cellular survival. As calculated, the enzyme molecules cover about 10% of cellular surface while inhibiting 90% of transmembrane transfer. The obtained data are considered to be a solid argument supporting the important role of the membrane phospholipids in the mechanism of cation-induced DNA transfer into the cell.


Analysis of tobacco color and location features using visible-near infrared hyperspectral data.
In the present paper, six categories of standard industrial grading tobacco provided by Hongta Group are taken as experimental samples, including three different tobacco locations-upper (B), middle(C) and lower(X) parts, with each part containing two kinds of tobacco colors-orange (O) and lemon yellow (L). Two methods including projection model method based on principal component and Fisher criterion (PPF) and support vector machine (SVM) method are used to analyze color and location features of tobacco based on visible-near infrared hyperspectral data. The results of projection model method indicate that in the projection and similarity analysis of tobacco color, location and six tobacco groups classified by color and location, two kinds of color can be fully differentiated, of which the similarity value is -1.000 8. Tobacco from upper and lower parts can also be fully differentiated with similarity value 0.405 3, but they both have intersections with tobac- co from middle part. Six tobacco groups classified by color and location can be fully differentiated as well and their projection positions meet the actual external features of tobacco. The results of support vector machine method indicate that in the discriminant analysis of tobacco color, location and six tobacco groups classified by color and location, the average recognition rate of tobacco colors reaches 98%. The average recognition rate of tobacco location is 96%. The average recognition rate of six tobacco groups is 94%. Therefore, it's feasible to analyze color and location features of tobacco using visible-near infrared hyperspectral data, which can provide reference for tobacco quality evaluation, computer-aided grading and tobacco intelligent acquisition, and also offers a new approach to the analysis of exterior features of other agricultural products.


Growth temperature can alter the temperature dependent stimulation of photosynthesis by elevated carbon dioxide in Albutilon theophrasti.
Stimulation of photosynthesis in response to elevated carbon dioxide concentration [CO2] in the short-term (min) should be highly temperature dependent at high photon flux. However, it is unclear if long-term (days, weeks) adaptation to a given growth temperature alters the temperature-dependent stimulation of photosynthesis to [CO2]. In velveltleaf (Albutilon theophrasti), the response of photosynthesis, determined as CO2 assimilation, was measured over a range of internal CO2 concentrations at 7 short-term measurement (12, 16, 20, 24, 28, 32, 36 degrees C) temperatures for each of 4 long-term growth (16, 20, 28 and 32 degrees C) temperatures. In vivo estimates of VCmax, the maximum RuBP saturated rate of carboxylation, and Jmax, the light-saturated rate of potential electron transport, were determined from gas exchange measurements for each temperature combination. Overall, previous exposure to a given growth temperature adjusted the optimal temperatures of Jmax and VCmax with subsequently greater enhancement of photosynthesis at elevated [CO2] (i.e., a greater enhancement of photosynthesis at elevated [CO2] was observed at low measurement temperatures for A. theophrasti grown at low growth temperatures compared with higher growth temperatures, and vice versa for plants grown and measured at high temperatures). Previous biochemical based models used to predict the interaction between rising [CO2] and temperature on photosynthesis have generally assumed no growth temperature effect on carboxylation kinetics or no limitation by Jmax. In the current study, these models over predicted the temperature dependence of the photosynthetic response to elevated [CO2] at temperatures above 24 degrees C. If these models are modified to include long-term adjustments of Jmax and VCmax to growth temperature, then greater agreement between observed and predicted values was obtained.


Multifocal Disease Progression and Subsequent Intervention in Patients with Actin Alpha-2 Variants; A Single Center Experience.
Describe patient characteristics and indications for surgical intervention, reoperation, and outcomes in patients with actin alpha-2 (ACTA2) variants. Single center retrospective cohort study with prospective follow-up was performed for 38 patients with an ACTA2 variant. From 1999-2020, twenty-six (70%) patients underwent surgery, 11 remain under surveillance (mean follow-up 7.5 ± 5 years). Median age at index operation was 42 (range 10-69) years, with 4 pediatric cases. Thoracic aortic aneurysm was present in 19 (73%) patients (mean adult max diameter 5.2 ± 0.8 cm, pediatric z-score 10.7 ± 5.4). Aortic dissection was present in 13 (50%) patients, with 4 (15%) having Type A dissection. Operations included replacement of the aortic root in 16 (17%), ascending aorta in 20 (77%), and aortic arch in 14 (54%) patients. Four (15%) patients had coronary artery disease (CAD), and 2 (7.7%) underwent concomitant coronary artery bypass grafting. There was no operative mortality, stroke, re-operation for bleeding, or dialysis-dependent renal failure; One (3.8%) patient developed acute on chronic kidney injury. Three patients (12%) required prolonged ventilation. Eleven (42%) patients underwent 26 reoperations, median time 45 (range 4-147) months, including 5 open thoracoabdominal aneurysm repairs. Patients with ACTA2 variants frequently develop aortic aneurysm and are at risk of aortic dissection and CAD. However, age at diagnosis and symptoms at presentation are highly variable. Multiple operations are often required for disease management, particularly after dissection. Close monitoring and timely intervention are important in mitigating disease progression and improving outcomes.


Laboratory testing and diagnostic coding for cytomegalovirus among privately insured infants in the United States: a retrospective study using administrative claims data.
Rates of laboratory testing and diagnostic practices for congenital CMV in the United States are unknown. We determined rates of CMV testing and diagnostic coding for CMV among insured infants in the United States using a national healthcare claims database. We analyzed medical claims from 2011 Truven Health MarketScan® Commercial databases for infants who were ≤30 days of age. We used ICD-9-CM codes to identify infants with CMV and CMV-associated conditions. We computed frequencies of infants with CPT codes for CMV testing. A total of 368,266 infants met the study criteria. We identified 61 (0.02%) infants with a diagnostic code for CMV. Among the 368,266 infants, 229 (0.1%) infants had a code for CMV-specific testing, of which 43% had codes for CMV polymerase chain reaction (PCR) and/or CMV direct florescent antibody (DFA) testing, 44% for CMV serologic testing alone, and 13% for CMV serology and non-specific PCR and/or culture. Over 80% (187/229) with CMV testing had a code for ≥1 CMV-associated conditions. Although infrequently coded for, CMV testing was more common among infants with a code for a condition possibly associated with CMV than infants without these conditions (0.14% (187/ 136,857) vs. 0.02% (42/231,409)). The low rates of CMV testing among infants with symptoms suggestive of congenital CMV infection and the substantial proportion of infants tested with only serologic assays instead of PCR or viral culture suggests gaps in awareness and knowledge of congenital CMV and its diagnosis among healthcare providers. Although claims databases presumably do not capture all diagnosed CMV cases or CMV-specific testing, healthcare claims are a potential source for surveillance and monitoring practices of CMV-specific testing and diagnostic coding for CMV among infants.


Therapeutic approaches to chronic lymphocytic leukemia.
Chronic lymphocytic leukemia is the most common leukemia in the Western Hemisphere and will increase in prevalence as the population continues to age. Partly because of the advanced age of patients and the often prolonged indolent course of disease, therapy has changed little over the past several decades. The clinical course is highly variable and several clinical features have prognostic value. Until recently, therapeutic approaches have ranged from watchful observation to palliative treatment with an alkylating agent alone or combined with a corticosteroid; however, a number of new chemotherapeutic agents (eg, fludarabine, deoxycoformycin, and chloride-oxyadenosine) have been shown to act effectively against the disease. The availability of effective new agents combined with a better understanding of the biology and prognostic determinants in this disease have sparked recent interest in the optimal management of patients with this increasingly common malignancy.


Occupational exposures and Parkinson's disease mortality in a prospective Dutch cohort.
We investigated the association between six occupational exposures (ie, pesticides, solvents, metals, diesel motor emissions (DME), extremely low frequency magnetic fields (ELF-MF) and electric shocks) and Parkinson's disease (PD) mortality in a large population-based prospective cohort study. The Netherlands Cohort Study on diet and cancer enrolled 58,279 men and 62,573 women aged 55-69 years in 1986. Participants were followed up for cause-specific mortality over 17.3 years, until December 2003, resulting in 402 male and 207 female PD deaths. Following a case-cohort design, a subcohort of 5,000 participants was randomly sampled from the complete cohort. Information on occupational history and potential confounders was collected at baseline. Job-exposure matrices were applied to assign occupational exposures. Associations with PD mortality were evaluated using Cox regression. Among men, elevated HRs were observed for exposure to pesticides (eg, ever high exposed, HR 1.27, 95% CI 0.86 to 1.88) and ever high exposed to ELF-MF (HR 1.54, 95% CI 1.00 to 2.36). No association with exposure duration or trend in cumulative exposure was observed for any of the occupational exposures. Results among women were unstable due to small numbers of high-exposed women. Associations with PD mortality were observed for occupational exposure to pesticides and ELF-MF. However, the weight given to these findings is limited by the absence of a monotonic trend with either duration or cumulative exposure. No associations were found between PD mortality and occupational exposure to solvents, metals, DME or electric shocks.


Genetic and Genomic Advances in Developmental Models: Applications for Nutrition Research.
There is increasing appreciation that dietary components influence and interact with genes important to metabolism. How such influences impact developmental regulation and programming or risks of chronic diseases remains unclear. Nutrition is recognized to affect development and chronic diseases, but our understanding about how genes essential to nutrient metabolism regulate development and impact risks of these diseases remains unclear. Historically, mammalian models, especially rodents such as rats and mice, have been the primary models used for nutrition and developmental nutrition science, although their complexity and relatively slow rate of development often compromise rapid progress in resolving fundamental, genetic-related questions. Accordingly, the objective of this review is to highlight the opportunities for developmental models in the context of uncovering the function of gene products that are relevant to human nutrition and provide the scientific bases for these opportunities. We present recent studies in zebrafish related to obesity as applications of developmental models in nutritional science. Although the control of external factors and dependent variables, such as nutrition, can be a challenge, suggestions for standardizations related to diet are made to improve consistency in findings between laboratories. The review also highlights the need for standardized diets across different developmental models, which could improve consistency in findings across laboratories. Alternative and developmental animal models have advantages and largely untapped potential for the advancement of nutrigenomics and nutritionally relevant research areas.


Immediate Weightbearing Following First Metatarsal Phalangeal Joint Arthrodesis With 2 Nickel Titanium Alloy Staples.
The use of staples has been shown to be a reasonable fixation technique to achieve stability of a first MTPJ arthrodesis. Although it has been shown to be a weaker construct than crossed screws or plate and screw combinations, their ease of insertion, low profile, and stability make them a desirable choice for first MTPJ arthrodesis fixation. However, because of this relative weakness, the question remains whether immediate weightbearing when using staples is advisable. The aim of this study is to determine whether the use of 2 nickel-titanium alloy (NITINOL) staples, placed at 90 degrees to one another is a stable enough construct to support full, immediate weightbearing following first MTPJ arthrodesis. We performed a retrospective chart review of patients undergoing first MTPJ arthrodesis by a single surgeon utilizing 2 NITINOL staples placed at 90 degrees to one another. Patients were allowed to be fully weightbearing immediately postoperatively. Forty-seven of 50 (94%) patients achieved complete radiologic consolidation of fusion at 12 weeks, with only 3 requiring revision surgery for nonunion. All of the patients requiring revision surgery for nonunion, had preoperative diagnosis of hallux abducto valgus. We concluded that the use of 2 NITINOL staples placed at 90 degrees to one another is a viable option for first MTPJ arthrodesis, and immediate weightbearing does not increase rate of nonunion or incidence of revision surgery when compared to other fixation techniques.


Cytogenetic biomonitoring in petrol station attendants: A micronucleus study.
Benzene, which is a major organic product, on chronic exposure can result in many malignant disorders, and therefore exposure to gasoline vapors is classified by the International Agency for Research of Cancer as possible carcinogenic to humans. Petrol station attendants are chronically exposed to petroleum derivatives through inhalation of petrol during vehicle refuelling. This study is aimed to investigate cytogenotoxic damage in exfoliated buccal cells obtained from petrol station workers and control subjects using micronucleus (MN) test. This study was carried out on 30 petrol station attendants working at different petrol stations located in Indore. The control group consisted of 30 healthy subjects who were not exposed to benzene. Buccal cell samples were collected at the end of the work shift. Slides were stained and were evaluated to determine the MN frequencies. Exposure monitoring was performed by the detection of phenol excreted in the urine. Urinary phenol measurements were performed following the colorimetric quantitative determination method of Yamaguchi and Hayashi. Variations in MN frequencies were seen in control and petrol bunk attendants. The MN test in exfoliated epithelial cells seems to be a useful biomarker of occupational exposure to genotoxic chemicals. Phenol is the principal metabolite of benzene. Therefore, phenol concentration in the urine of exposed workers can be used as a biomarker of external exposure.


Measuring case severity: a novel tool for benchmarking and clinical documentation improvement.
Severity of illness (SOI) is an All Patients Refined Diagnosis Related Groups (APR DRG) modifier based on comorbidity capture. Tracking SOI helps hospitals improve performance and resource distribution. Furthermore, benchmarking SOI plays a key role in Quality Improvement (QI) efforts such as Clinical Documentation Improvement (CDI) programs. The current SOI system highly relies on the 3 M APR DRG grouper that is updated annually, making it difficult to track severity longitudinally and benchmark against hospitals with different patient populations. Here, we describe an alternative SOI scoring system that is grouper-independent and that can be tracked longitudinally. Admission data for 2019-2020 U.S. News and World Report Honor Roll facilities were downloaded from the Vizient Clinical Database and split into training and testing datasets. Elixhauser comorbidities, body systems developed from the Healthcare Cost and Utilization Project (HCUP), and ICD-10-CM complication and comorbidity (CC/MCC) indicators were selected as the predictors for orthogonal polynomial regression models to predict patients' admission and discharge SOI. Receiver operating characteristic (ROC) and Precision-Recall (PR) analysis, and prediction accuracy were used to evaluate model performance. In the training dataset, the full model including both Elixhauser comorbidities and body system CC/MCC indicators had the highest ROC AUC, PR AUC and predication accuracy for both admission (ROC AUC: 92.9%; PR AUC: 91.0%; prediction accuracy: 85.4%) and discharge SOI (ROC AUC: 93.6%; PR AUC: 92.8%; prediction accuracy: 86.2%). The model including only body system CC/MCC indicators had similar performance for admission (ROC AUC: 92.4%; PR AUC: 90.4%; prediction accuracy: 84.8%) and discharge SOI (ROC AUC: 93.1%; PR AUC: 92.2%; prediction accuracy: 85.6%) as the full model. The model including only Elixhauser comorbidities exhibited the lowest performance. Similarly, in the validation dataset, the prediction accuracy was 86.2% for the full model, 85.6% for the body system model, and 79.3% for the comorbidity model. With fewer variables and less model complexity, the body system model was more efficient and was determined to be the optimal model. The probabilities generated from this model, named J_Score and J_Score_POA, successfully measured SOI and had practical applications in assessment of CDI performance. The J_Scores generated from the body system model have significant value in evaluating admission and discharge severity of illness. We believe that this new scoring system will provide a useful tool for healthcare institutions to benchmark patients' illness severity and augment Quality Improvement (QI) efforts.


Perinatal Women's Perspectives of, and Engagement in, Digital Emotional Well-Being Training: Mixed Methods Study.
Psychological distress in the early postpartum period can have long-lasting deleterious effects on a mother's well-being and negatively affect her infant's development. Intervention approaches based in contemplative practices such as mindfulness and loving-kindness and compassion are intended to alleviate distress and cultivate well-being and can be delivered effectively as digital mental health interventions (DMHIs). To understand the feasibility of engaging perinatal women in digital interventions, this study aimed to document participants' experiences in the Mums Minds Matter (MMM) study, a pilot randomized controlled trial comparing mindfulness, loving-kindness and compassion, and progressive muscle relaxation training delivered in a digital format and undertaken during pregnancy. To assess the different stages of engagement during and after the intervention, we adapted the connect, attend, participate, enact (CAPE) framework that is based on the idea that individuals go through different stages of engagement before they are able to enact change. The MMM study was nested within a longitudinal birth cohort, The ORIGINS Project. We aimed to recruit 25 participants per randomization arm. Data were collected sequentially during the intervention through regular web-based surveys over 8 weeks, with opportunities to provide regular feedback. In the postintervention phase, qualitative data were collected through purposive sampling. Of 310 eligible women, 84 (27.1% [connect rate]) enrolled to participate in MMM. Of the remaining 226 women who did not proceed to randomization, 223 (98.7%) failed to complete the baseline surveys and timed out of eligibility (after 30 weeks' gestation), and 3 (1.3%) displayed high psychological distress scores. Across all program groups, 17 (20% [attend rate]) of the 84 participants actively opted out, although more may have disengaged from the intervention but did not withdraw. The main reasons for withdrawal were busy life and other priorities. In this study, we assessed active engagement and ongoing skills use (participate and enact) through postintervention interviews. We undertook 15 participant interviews, conducted 1 month to 3 months after the intervention. Our results provide insights into participant barriers and enablers as well as app changes, such as the ability to choose topics, daily reminders, case studies, and diversity in sounds. Implementing a DMHI that is brief, includes frequent prompts or nudges, and is easily accessible is a key strategy to target perinatal women. Our research will enable future app designs that are sufficiently nuanced to maximize the uptake, engagement, and application of mental health skills and contemplative practices in the perinatal period. Providing convenient access to engaging and effective prevention programs is critical and should be part of prenatal self-care. Our research underscores the appeal and feasibility of digital intervention approaches based in contemplative practices for perinatal women. Australian New Zealand Clinical Trials Registry (ANZCTR) 12620000672954p; https://anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12620000672954p. RR2-10.2196/19803.


Multiple DNA processing reactions underlie Tn7 transposition.
The bacterial transposon Tn7 uses a cut and paste mechanism to translocate between non-homologous insertion sites. In the first step of recombination, double-strand breaks at each transposon end disconnect the element from the donor backbone; in the second step, the now exposed 3' transposon ends join to the target DNA. To dissect the chemical steps in these reactions, we have used mutant transposons altered at and near their extreme termini. We find that the initiating double-strand breaks result from a collaboration of two distinct DNA strand processing activities, one mediating cleavages at the 3' ends of Tn7, which can be blocked by changes at the transposon tips, and another mediating cleavages at the 5' ends. The joining of exposed 3'transposon ends to the target DNA can be blocked by changing the transposon tips. Our results suggest that the target joining step occurs through two usually concerted, but actually separable, reactions in which individual 3' transposon ends are joined to separate strands of the target DNA. Thus Tn7 transposition involves several distinct DNA processing reactions: strand cleavage and strand transfer reactions at the 3' ends of the transposon, and separate strand cleavage reactions at the 5' ends of the transposon.


Pathogenic role of Fgf23 in Dmp1-null mice.
Autosomal recessive hypophosphatemic rickets (ARHR), which is characterized by renal phosphate wasting, aberrant regulation of 1alpha-hydroxylase activity, and rickets/osteomalacia, is caused by inactivating mutations of dentin matrix protein 1 (DMP1). ARHR resembles autosomal dominant hypophosphatemic rickets (ADHR) and X-linked hypophosphatemia (XLH), hereditary disorders respectively caused by cleavage-resistant mutations of the phosphaturic factor FGF23 and inactivating mutations of PHEX that lead to increased production of FGF23 by osteocytes in bone. Circulating levels of FGF23 are increased in ARHR and its Dmp1-null mouse homologue. To determine the causal role of FGF23 in ARHR, we transferred Fgf23 deficient/enhanced green fluorescent protein (eGFP) reporter mice onto Dmp1-null mice to create mice lacking both Fgf23 and Dmp1. Dmp1(-/-) mice displayed decreased serum phosphate concentrations, inappropriately normal 1,25(OH)(2)D levels, severe rickets, and a diffuse form of osteomalacia in association with elevated Fgf23 serum levels and expression in osteocytes. In contrast, Fgf23(-/-) mice had undetectable serum Fgf23 and elevated serum phosphate and 1,25(OH)(2)D levels along with severe growth retardation and focal form of osteomalacia. In combined Dmp1(-/-)/Fgf23(-/-), circulating Fgf23 levels were also undetectable, and the serum levels of phosphate and 1,25(OH)(2)D levels were identical to Fgf23(-/-) mice. Rickets and diffuse osteomalacia in Dmp1-null mice were transformed to severe growth retardation and focal osteomalacia characteristic of Fgf23-null mice. These data suggest that the regulation of extracellular matrix mineralization by DMP1 is coupled to renal phosphate handling and vitamin D metabolism through a DMP1-dependent regulation of FGF23 production by osteocytes.


Becoming a better person: temporal remoteness biases autobiographical memories for moral events.
Our autobiographical self depends on the differential recollection of our personal past, notably including memories of morally laden events. Whereas both emotion and temporal recency are well known to influence memory, very little is known about how we remember moral events, and in particular about the distribution in time of memories for events that were blameworthy or praiseworthy. To investigate this issue in detail, we collected a novel database of 758 confidential, autobiographical narratives for personal moral events from 100 well-characterized healthy adults. Negatively valenced moral memories were significantly more remote than positively valenced memories, both as measured by the valence of the cue word that evoked the memory as well as by the content of the memory itself. The effect was independent of chronological age, ethnicity, gender or personality, arguing for a general emotional bias in how we construct our moral autobiography.


Suppression of the humoral antibody response in natural retrovirus infections.
The feline leukemia virus (FeLV) frequently causes death by predisposing the host to acute infections by other pathogens rather than by inducing leukemia. In a previous study, cats infected with FeLV were found to have prolonged homograft rejection responses but there was no evidence that the humoral immune response was impaired. In the present study, the humoral response to the synthetic multichain polypeptide (L-tyrosine-L-glutamic acid)-poly-DL-alanine-poly-L-lysine, denoted (T.G)AL, was found to be significantly depressed in healthy cats that were naturally infected with FeLV compared to uninfected controls. In cats with persistent FeLV viremia the major antibody response to (T.G)AL, normally seen at days 9 to 14 after immunization, was both delayed and greatly reduced.


Exploring the origin of the directional emission from a microcavity with a large-aperture surface-emitting laser.
The origin of the direction emission from a microcavity is investigated with a large-aperture surface-emitting laser with an equilateral-triangular shape. Experimental results reveal that a wide-spread eigenmode and a localized superscar mode can display quite similar far-field directional emissions. This experimental finding is theoretically confirmed with the quantum-billiard wave function and the approximation of the paraxial propagation.


Diversity and applications of Bacillus bacteriocins.
Members of the genus Bacillus are known to produce a wide arsenal of antimicrobial substances, including peptide and lipopeptide antibiotics, and bacteriocins. Many of the Bacillus bacteriocins belong to the lantibiotics, a category of post-translationally modified peptides widely disseminated among different bacterial clades. Lantibiotics are among the best-characterized antimicrobial peptides at the levels of peptide structure, genetic determinants and biosynthesis mechanisms. Members of the genus Bacillus also produce many other nonmodified bacteriocins, some of which resemble the pediocin-like bacteriocins of the lactic acid bacteria (LAB), while others show completely novel peptide sequences. Bacillus bacteriocins are increasingly becoming more important due to their sometimes broader spectra of inhibition (as compared with most LAB bacteriocins), which may include Gram-negative bacteria, yeasts or fungi, in addition to Gram-positive species, some of which are known to be pathogenic to humans and/or animals. The present review provides a general overview of Bacillus bacteriocins, including primary structure, biochemical and genetic characterization, classification and potential applications in food preservation as natural preservatives and in human and animal health as alternatives to conventional antibiotics. Furthermore, it addresses their environmental applications, such as bioprotection against the pre- and post-harvest decay of vegetables, or as plant growth promoters.


The Effect of Temperature on Microtubule-Based Transport by Cytoplasmic Dynein and Kinesin-1 Motors.
Cytoplasmic dynein and kinesin are both microtubule-based molecular motors but are structurally and evolutionarily unrelated. Under standard conditions, both move with comparable unloaded velocities toward either the microtubule minus (dynein) or plus (most kinesins) end. This similarity is important because it is often implicitly incorporated into models that examine the balance of cargo fluxes in cells and into models of the bidirectional motility of individual cargos. We examined whether this similarity is a robust feature, and specifically whether it persists across the biologically relevant temperature range. The velocity of mammalian cytoplasmic dynein, but not of mammalian kinesin-1, exhibited a break from simple Arrhenius behavior below 15°C-just above the restrictive temperature of mammalian fast axonal transport. In contrast, the velocity of yeast cytoplasmic dynein showed a break from Arrhenius behavior at a lower temperature (∼8°C). Our studies implicate cytoplasmic dynein as a more thermally tunable motor and therefore a potential thermal regulator of microtubule-based transport. Our theoretical analysis further suggests that motor velocity changes can lead to qualitative changes in individual cargo motion and hence net intracellular cargo fluxes. We propose that temperature can potentially be used as a noninvasive probe of intracellular transport.


Skin care education and individual counselling versus treatment as usual in healthcare workers with hand eczema: randomised clinical trial.
To evaluate the effect of a secondary prevention programme with education on skin care and individual counselling versus treatment as usual in healthcare workers with hand eczema. Randomised, observer blinded parallel group superiority clinical trial. Three hospitals in Denmark. 255 healthcare workers with self reported hand eczema within the past year randomised centrally and stratified by profession, severity of eczema, and hospital. 123 were allocated to the intervention group and 132 to the control group. Education in skin care and individual counselling based on patch and prick testing and assessment of work and domestic related exposures. The control was treatment as usual. The primary outcome was clinical severity of disease at five month follow-up measured by scores on the hand eczema severity index. The secondary outcomes were scores on the dermatology life quality index, self evaluated severity of hand eczema, skin protective behaviours, and knowledge of hand eczema from onset to follow-up. Follow-up data were available for 247 of 255 participants (97%). At follow-up, the mean score on the hand eczema severity index was significantly lower (improved) in the intervention group than control group: difference of means, unadjusted -3.56 (95% confidence interval -4.92 to -2.14); adjusted -3.47 (-4.80 to -2.14), both P<0.001 for difference. The mean score on the dermatology life quality index was also significantly lower (improved) in the intervention group at follow-up: difference of means: unadjusted -0.78, non-parametric test P=0.003; adjusted -0.92, -1.48 to -0.37). Self evaluated severity and skin protective behaviour by hand washings and wearing of protective gloves were also statistically significantly better in the intervention group, whereas this was not the case for knowledge of hand eczema. A secondary prevention programme for hand eczema improved severity and quality of life and had a positive effect on self evaluated severity and skin protective behaviour by hand washings and wearing of protective gloves. ClinicalTrials.gov NCT01012453.


Dr-MUSIC: An Effective Device for Investigating Multisensory Mechanisms during Development with EEG recordings.
From birth, we are continuously exposed to multisensory stimuli that we learn to select and integrate during development to perceive a coherent world. To date, there are no optimal solutions to investigate how auditory, visual and tactile signals are integrated during EEG recording in infants and children. The present work aims to introduce Dr-MUSIC, a novel multisensory device with EEG-compatible timing and an attractive design for children. It is composed of audio, visual, and tactile stimulators arranged in the form of a couple of chubby dragons that can simultaneously provide selectable uni-, bi-, or tri-modal information. We first validated the system's EEG compatibility in 8 adults by implementing an audio-tactile oddball task during a high-density EEG recording. Then, we replicated the same task in a couple of toddlers to validate the device's usability for young children. The results suggest that the system can be effectively used for setting new experimental protocols to understand the neural basis of multisensory integration in the first years of life.Clinical Relevance- The amusing design and the possibility of changing the stimulation's characteristics (i.e., light, sound, and vibrotactile features) make it attractive in children with and without sensory impairments. Therefore, Dr-MUSIC could be used to investigate multisensory development and related neural correlates in typical and atypical children to design new early rehabilitation protocols.


Toward an experimental chiropractic: time-series designs.
If chiropractic is to develop as a clinical science, it must develop an experimental data-base. Despite numerous continuing obstacles, a growing segment of the profession is advocating chiropractic clinical trials. However, the large-scale control-group clinical-experimental designs which have most frequently been recommended are usually beyond the economic means of chiropractic institutions. Moreover, such designs are impractical in many ways for the chiropractic field-doctor who wishes to integrate the roles of scientist and practitioner. Time-series experimental (and case study) designs offer practical and economical alternatives for the DC, whether inter, solo-practitioner, or academic researcher. Several types of time-series designs are described, published examples from related health-care literature are noted, and the role of time-series research in furthering the goals of chiropractic research are reviewed. Ethical considerations in clinical research are briefly noted.


Stay hydrated: basolateral fluids shaping tissues.
During development, embryos perform a mesmerizing choreography, which is crucial for the correct shaping, positioning and function of all organs. The cellular properties powering animal morphogenesis have been the focus of much attention. In contrast, much less consideration has been given to the invisible engine constituted by the intercellular fluid. Cells are immersed in fluid, of which the composition and physical properties have a considerable impact on development. In this review, we revisit recent studies from the perspective of the fluid, focusing on basolateral fluid compartments and taking the early mouse and zebrafish embryos as models. These examples illustrate how the hydration levels of tissues are spatio-temporally controlled and influence embryonic development.


Na+ /H+ exchange via the Drosophila vesicular glutamate transporter mediates activity-induced acid efflux from presynaptic terminals.
Intracellular pH regulation is vital to neurons as nerve activity produces large and rapid acid loads in presynaptic terminals. Rapid clearance of acid loads is necessary to maintain control of neurotransmission, but neuronal acid clearance mechanisms remain poorly understood. Glutamate is loaded into synaptic vesicles via the vesicular glutamate transporter (VGLUT), a mechanism conserved across phyla, and this study reports a previously unknown role for VGLUT as an acid-extruding protein when deposited in the plasmamembrane during exocytosis. The finding was made in Drosophila (fruit fly) larval motor neurons through a combined pharamacological and genetic dissection of presynaptic pH homeostatic mechanisms. A dual role for VGLUT serves to integrate neuronal activity and pH regulation in presynaptic nerve terminals. Neuronal activity can result in transient acidification of presynaptic terminals, and such shifts in cytosolic pH (pHcyto ) probably influence mechanisms underlying forms of synaptic plasticity with a presynaptic locus. As neuronal activity drives acid loading in presynaptic terminals, we hypothesized that the same activity might drive acid efflux mechanisms to maintain pHcyto homeostasis. To better understand the integration of neuronal activity and pHcyto regulation we investigated the acid extrusion mechanisms at Drosophila glutamatergic motorneuron terminals. Expression of a fluorescent genetically encoded pH indicator, named 'pHerry', in the presynaptic cytosol revealed acid efflux following nerve activity to be greater than that predicted from measurements of the intrinsic rate of acid efflux. Analysis of activity-induced acid transients in terminals deficient in either endocytosis or exocytosis revealed an acid efflux mechanism reliant upon synaptic vesicle exocytosis. Pharmacological and genetic dissection in situ and in a heterologous expression system indicate that this acid efflux is mediated by conventional plasmamembrane acid transporters, and also by previously unrecognized intrinsic H+ /Na+ exchange via the Drosophila vesicular glutamate transporter (DVGLUT). DVGLUT functions not only as a vesicular glutamate transporter but also serves as an acid-extruding protein when deposited on the plasmamembrane.


Stable transfer of an optical frequency standard via a 4.6 km optical fiber.
We present a technique for the stable transfer of an optical frequency reference over a kilometer-scale optical fiber link. This technique implements phase measurements and laser feedback to cancel out the phase fluctuations that are introduced to an optical frequency standard as it passes through the fiber. We also present results for a bench top experiment, developed for the Advanced LIGO lock acquisition system, where this technique is implemented to phase-lock two Nd:YAG lasers, through a 4.6 km optical fiber. The resulting differential optical frequency noise reaches a level as low as 0.5 mHz/ radical Hz for Fourier frequencies between 5 Hz and 20 Hz, which is equal to a fractional frequency stability of 1.7 x 10(-18)/ radical Hz.


Directing assembly of DNA-coated colloids with magnetic fields to generate rigid, semiflexible, and flexible chains.
We report the formation of colloidal macromolecules consisting of chains of micron-sized paramagnetic particles assembled using a magnetic field and linked with DNA. The interparticle spacing and chain flexibility were controlled by varying the magnetic field strength and the linker spring constant. Variations in the DNA lengths allowed for the generation of chains with an improved range of flexibility as compared to previous studies. These chains adopted the rigid-rod, semiflexible, and flexible conformations that are characteristic of linear polymer systems. These assembly techniques were investigated to determine the effects of the nanoscale DNA linker properties on the properties of the microscale colloidal chains. With stiff DNA linkers (564 base pairs) the chains were only stable at moderate to high field strengths and produced rigid chains. For flexible DNA linkers (8000 base pairs), high magnetic field strengths caused the linkers to be excluded from the gap between the particles, leading to a transition from very flexible chains at low field strengths to semiflexible chains at high field strengths. In the intermediate range of linker sizes, the chains exhibited predictable behavior, demonstrating increased flexibility with longer DNA linker length or smaller linking field strengths. This study provides insight into the process of directed assembly using magnetic fields and DNA by precisely tuning the components to generate colloidal analogues of linear macromolecular chains.